The domestic pig as a translational model of hyperoxaluria: a pilot study of acute and chronic sodium oxalate infusion

Tomasz Jacek^1*Dominika Szkopek²Piotr Wychowanski^3,4Janine Donaldson⁵Kamil Zaworski⁶Mariusz Strutyński⁷Siarhei Kirko⁷Olena Prykhodko^8,9Olexandr Fedkiv^8,9Stefan G Pierzynowski^10,7,8Kateryna Pierzynowska^6,7,8*

• ¹Instytut Zootechniki Panstwowy Instytut Badawczy, Kraków, Poland
• ²Large Animal Models Laboratory, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jabłonna, Poland
• ³Catholic University of the “Sacred Heart”, Department of Head and Neck and Sensory Organs, Rome, Italy
• ⁴Department of Interventional Dentistry, Collegium Medicum, Nicolaus Copernicus University,, Bydgoszcz, Poland
• ⁵Department of Physiology, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand,, Johannesburg, South Africa
• ⁶Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jabłonna, Poland
• ⁷Anara AB, Trelleborg, Sweden
• ⁸Department of Biology, Lund University, Lund, Sweden
• ⁹Division of Food and Pharma, Department of Process and Life Science Engineering, Lund University, Lund, Sweden
• ¹⁰Department of Medical Biology, Institute of Rural Health, Lublin, Poland

The purpose of this pilot study was to develop and characterize an in vivo porcine model of hyperoxaluria using intravenous infusion of sodium oxalate (NaOx). 2 experimental regimens were developed to replicate acute and follow up chronic hyperoxaluria. In the acute model, 3 different doses of 1% NaOx were administered over 15 hours, resulting in a dose-dependent increase in plasma oxalate concentration (Cmax: 42.4-122.4 µM) and transient hyperoxaluria, with a return to baseline values 6-8 hours after stopping the infusion of NaOx solution. In the chronic model, repeated infusions of NaOx for 7-11 days directly after acute tests led to persistent hyperoxalemia (up to 302.4 µM), clinical deterioration and dose-dependent calcium oxalate (CaOx) deposits in renal tissue (1.85%-9.55% of renal surface area), consistent with impaired renal function. The model represents the key clinical features of both rapidly inducible and reversible hyperoxalemia and hyperoxaluria, as well as the progressive nephrocalcinosis. Due to the physiological similarity between pigs and humans, the proposed porcine model could be considered as a quick and valuable tool for studying the pathophysiology of oxalate excess and testing the efficacy of new therapies to counteract its toxicity.